{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T02:05:04Z","timestamp":1787709904128,"version":"build-2784847793"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Macrophages drive the pathological process of inflammatory bowel diseases (IBD) mostly by secreting proinflammatory cytokines, such as Tnf-\u03b1. Recent studies have indicated the association between epigenetic modifications and macrophage functions. However, epigenetic mechanisms regulating macrophages\u2019 functional involvement in IBD remain unknown. In this study, we investigated whether the epigenetic regulator Uhrf1 plays a role in innate immunity by functionally regulating macrophages in intestines. We employed two transgenic strains of mice (one with Uhrf1 deficiency in macrophages [Uhrf1fl\/flLyz2-Cre mice] and the other with the two mutations at Uhrf1\u2019s DNA methylation regulatory site [Uhrf1YP187\/188AA mice]) to assess their susceptibility to dextran sodium sulfate\u2013induced colitis. We examined the cytokines derived from Uhrf1fl\/flLyz2-Cre and Uhrf1YP187\/188AA macrophages in response to LPS stimulation. We also analyzed the effects of proinflammatory cytokines on Uhrf1 expression in macrophages. The data demonstrated that Uhrf1 deficiency and Uhrf1YP187\/188AA mutation resulted in severe colitis in the dextran sodium sulfate\u2013treated mice. In vitro analysis revealed the hypomethylation of Tnf-\u03b1 promoter and the increased Tnf-\u03b1 expression in Uhrf1fl\/flLyz2-Cre and Uhrf1YP187\/188AA macrophages in response to LPS stimulation, and anti\u2013Tnf-\u03b1 therapy implied the key role of Tnf-\u03b1 to the aggravated colitis in Uhrf1-deficient mice. Exogenous Tnf-\u03b1 destabilized Uhrf1 protein through ubiquitination-mediated protein degradation, triggering macrophage activation. In conclusion, we identified that Uhrf1-mediated DNA methylation controls Tnf-\u03b1 expression of macrophages in the experimental colitis resembling IBD. The epigenetic mechanisms that activate macrophages may provide new therapeutic targets for IBD treatment.<\/jats:p>","DOI":"10.4049\/jimmunol.1900467","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T19:25:13Z","timestamp":1571081113000},"page":"3045-3053","source":"Crossref","is-referenced-by-count":34,"title":["Uhrf1-Mediated Tnf-\u03b1 Gene Methylation Controls Proinflammatory Macrophages in Experimental Colitis Resembling Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"203","author":[{"given":"Shanshan","family":"Qi","sequence":"first","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkui","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxi","family":"Xiang","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobin","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]},{"name":"Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]},{"name":"Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-0728","authenticated-orcid":false,"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]},{"name":"Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,1]]},"reference":[{"key":"2025030417544388300_r1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1056\/NEJMra020831","article-title":"Inflammatory bowel disease","volume":"347","author":"Podolsky","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"2025030417544388300_r2","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.2174\/13816128113199990416","article-title":"Inflammatory bowel disease: etiology, pathogenesis and current therapy","volume":"20","author":"Ko","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"2025030417544388300_r3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"Xavier","year":"2007","journal-title":"Nature"},{"key":"2025030417544388300_r4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nri3430","article-title":"Role of the gut microbiota in immunity and inflammatory disease","volume":"13","author":"Kamada","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"2025030417544388300_r5","first-page":"328","article-title":"Inflammatory bowel disease: the classic gastrointestinal autoimmune disease","volume":"44","author":"Kaistha","year":"2014","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"2025030417544388300_r6","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1084\/jem.161.3.475","article-title":"Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4\/80","volume":"161","author":"Lee","year":"1985","journal-title":"J. Exp. Med."},{"key":"2025030417544388300_r7","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1365-3083.2009.02319.x","article-title":"Mucosal immunity: induction, dissemination, and effector functions","volume":"70","author":"Brandtzaeg","year":"2009","journal-title":"Scand. J. Immunol."},{"key":"2025030417544388300_r8","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/mi.2012.89","article-title":"Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors","volume":"6","author":"Bain","year":"2013","journal-title":"Mucosal Immunol."},{"key":"2025030417544388300_r9","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/j.1365-2249.1991.tb05757.x","article-title":"Changes in phenotypically distinct mucosal macrophage populations may be a prerequisite for the development of inflammatory bowel disease","volume":"85","author":"Allison","year":"1991","journal-title":"Clin. Exp. Immunol."},{"key":"2025030417544388300_r10","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1023\/A:1021960401290","article-title":"Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice","volume":"48","author":"Watanabe","year":"2003","journal-title":"Dig. Dis. Sci."},{"key":"2025030417544388300_r11","doi-asserted-by":"crossref","first-page":"G770","DOI":"10.1152\/ajpgi.00453.2007","article-title":"Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus","volume":"294","author":"Ghia","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2025030417544388300_r12","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1002\/jcp.24939","article-title":"Epoxyeicosatrienoic acids regulate macrophage polarization and prevent LPS-induced cardiac dysfunction","volume":"230","author":"Dai","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"2025030417544388300_r13","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1002\/eji.201141792","article-title":"Epigenetic control of macrophage polarization","volume":"41","author":"Takeuch","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"2025030417544388300_r14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0078045","article-title":"Cytokine induced phenotypic and epigenetic signatures are key to establishing specific macrophage phenotypes","volume":"8","author":"Kittan","year":"2013","journal-title":"PLoS One"},{"key":"2025030417544388300_r15","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.toxlet.2013.12.023","article-title":"SOCS1 hypermethylation mediated by DNMT1 is associated with lipopolysaccharide-induced inflammatory cytokines in macrophages","volume":"225","author":"Cheng","year":"2014","journal-title":"Toxicol. Lett."},{"key":"2025030417544388300_r16","doi-asserted-by":"crossref","first-page":"30053","DOI":"10.1038\/srep30053","article-title":"DNMT1-PPAR\u03b3 pathway in macrophages regulates chronic inflammation and atherosclerosis development in mice","volume":"6","author":"Yu","year":"2016","journal-title":"Sci. Rep."},{"key":"2025030417544388300_r17","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.87748","article-title":"Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity","volume":"1","author":"Wang","year":"2016","journal-title":"JCI Insight"},{"key":"2025030417544388300_r18","first-page":"3094","article-title":"Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury","volume":"128","author":"Thangavel","year":"2015","journal-title":"J. Cell Sci."},{"key":"2025030417544388300_r19","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ng.717","article-title":"Genome-wide meta-analysis increases to 71 the number of confirmed Crohn\u2019s disease susceptibility loci","volume":"42","author":"Franke","year":"2010","journal-title":"Nat. Genet."},{"key":"2025030417544388300_r20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease","volume":"491","author":"Jostins","year":"2012","journal-title":"Nature"},{"key":"2025030417544388300_r21","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.1147939","article-title":"UHRF1 plays a role in maintaining DNA methylation in mammalian cells","volume":"317","author":"Bostick","year":"2007","journal-title":"Science"},{"key":"2025030417544388300_r22","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/nature06397","article-title":"The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA","volume":"450","author":"Sharif","year":"2007","journal-title":"Nature"},{"key":"2025030417544388300_r23","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature12488","article-title":"Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication","volume":"502","author":"Nishiyama","year":"2013","journal-title":"Nature"},{"key":"2025030417544388300_r24","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nsmb.2391","article-title":"Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation","volume":"19","author":"Rothbart","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2025030417544388300_r25","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1101\/gad.220467.113","article-title":"Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation","volume":"27","author":"Rothbart","year":"2013","journal-title":"Genes Dev."},{"key":"2025030417544388300_r26","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/ncomms2562","article-title":"UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9","volume":"4","author":"Liu","year":"2013","journal-title":"Nat. Commun."},{"key":"2025030417544388300_r27","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.med.51.1.289","article-title":"Role of cytokines in the pathogenesis of inflammatory bowel disease","volume":"51","author":"Papadakis","year":"2000","journal-title":"Annu. Rev. Med."},{"key":"2025030417544388300_r28","doi-asserted-by":"crossref","first-page":"G367","DOI":"10.1152\/ajpgi.00173.2003","article-title":"TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation","volume":"286","author":"Ma","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2025030417544388300_r29","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0016-5085(99)70332-X","article-title":"Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn\u2019s disease","volume":"117","author":"Rutgeerts","year":"1999","journal-title":"Gastroenterology"},{"key":"2025030417544388300_r30","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0140-6736(02)08512-4","article-title":"Maintenance infliximab for Crohn\u2019s disease: the ACCENT I randomised trial","volume":"359","author":"Hanauer","year":"2002","journal-title":"Lancet"},{"key":"2025030417544388300_r31","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1365-2567.2006.02349.x","article-title":"The specific JNK inhibitor SP600125 targets tumour necrosis factor-alpha production and epithelial cell apoptosis in acute murine colitis","volume":"118","author":"Assi","year":"2006","journal-title":"Immunology"},{"key":"2025030417544388300_r32","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1053\/j.gastro.2010.04.006","article-title":"Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis","volume":"139","author":"Munitz","year":"2010","journal-title":"Gastroenterology"},{"key":"2025030417544388300_r33","article-title":"Investigation of macrophage polarization using bone marrow derived macrophages","volume":"76","author":"Ying","year":"2013","journal-title":"J. Vis. Exp."},{"key":"2025030417544388300_r34","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1038\/nprot.2007.315","article-title":"Isolation and subsequent analysis of murine lamina propria mononuclear cells from colonic tissue","volume":"2","author":"Weigmann","year":"2007","journal-title":"Nat. Protoc."},{"key":"2025030417544388300_r35","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.immuni.2013.08.025","article-title":"Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2","volume":"39","author":"Cui","year":"2013","journal-title":"Immunity"},{"key":"2025030417544388300_r36","first-page":"238","article-title":"Clinicopathologic study of dextran sulfate sodium experimental murine colitis","volume":"69","author":"Cooper","year":"1993","journal-title":"Lab. Invest."},{"key":"2025030417544388300_r37","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/0016-5085(90)90290-H","article-title":"A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice","volume":"98","author":"Okayasu","year":"1990","journal-title":"Gastroenterology"},{"key":"2025030417544388300_r38","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jcmgh.2015.01.006","article-title":"Experimental models of inflammatory bowel diseases","volume":"1","author":"Kiesler","year":"2015","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"2025030417544388300_r39","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2025030417544388300_r40","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.bcp.2006.07.010","article-title":"Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity","volume":"72","author":"Doyle","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"2025030417544388300_r41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1172\/JCI11837","article-title":"Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity","volume":"107","author":"Zhang","year":"2001","journal-title":"J. Clin. Invest."},{"key":"2025030417544388300_r42","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1136\/gut.2003.036632","article-title":"Downregulation of epithelial apoptosis and barrier repair in active Crohn\u2019s disease by tumour necrosis factor alpha antibody treatment. [Published erratum appears in 2004 Gut 53: 1722.]","volume":"53","author":"Zeissig","year":"2004","journal-title":"Gut"},{"key":"2025030417544388300_r43","doi-asserted-by":"crossref","first-page":"12464","DOI":"10.1038\/ncomms12464","article-title":"Dissecting the precise role of H3K9 methylation in crosstalk with DNA maintenance methylation in mammals","volume":"7","author":"Zhao","year":"2016","journal-title":"Nat. Commun."},{"key":"2025030417544388300_r44","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/ni.2886","article-title":"The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells","volume":"15","author":"Obata","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025030417544388300_r45","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1042\/BJ20100840","article-title":"UHRF1 depletion causes a G2\/M arrest, activation of DNA damage response and apoptosis","volume":"435","author":"Tien","year":"2011","journal-title":"Biochem. J."},{"key":"2025030417544388300_r46","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1056\/NEJM199710093371502","article-title":"A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn\u2019s disease. Crohn\u2019s disease cA2 study group","volume":"337","author":"Targan","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"2025030417544388300_r47","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jconrel.2010.10.002","article-title":"Oral TNF-\u03b1 gene silencing using a polymeric microsphere-based delivery system for the treatment of inflammatory bowel disease","volume":"150","author":"Kriegel","year":"2011","journal-title":"J. Control. Release"},{"key":"2025030417544388300_r48","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrgastro.2015.135","article-title":"Biologic agents for IBD: practical insights","volume":"12","author":"Danese","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2025030417544388300_r49","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1073\/pnas.1424089112","article-title":"Epigenetic control of intestinal barrier function and inflammation in zebrafish","volume":"112","author":"Marjoram","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030417544388300_r50","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"2025030417544388300_r51","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrg816","article-title":"The fundamental role of epigenetic events in cancer","volume":"3","author":"Jones","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"2025030417544388300_r52","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1038\/sj.onc.1210855","article-title":"The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression","volume":"27","author":"Achour","year":"2008","journal-title":"Oncogene"},{"key":"2025030417544388300_r53","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.07288","article-title":"Identification of polarized macrophage subsets in zebrafish","volume":"4","author":"Nguyen-Chi","year":"2015","journal-title":"eLife"},{"key":"2025030417544388300_r54","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S0016-5085(97)70030-1","article-title":"Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease","volume":"112","author":"Rugtveit","year":"1997","journal-title":"Gastroenterology"},{"key":"2025030417544388300_r55","doi-asserted-by":"crossref","first-page":"E9192","DOI":"10.1073\/pnas.1810584115","article-title":"Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death","volume":"115","author":"Garcia-Carbonell","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/203\/11\/3045\/61419697\/ji1900467.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/203\/11\/3045\/61419697\/ji1900467.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T19:23:57Z","timestamp":1741116237000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/203\/11\/3045\/7952369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,1]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,12,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1900467","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,12]]},"published":{"date-parts":[[2019,12,1]]}}}